Here's an excerpt dated 5/7/2015 Seeking Alpha. He's is questioned whether new data in "real-time" will be discussed in their pre-NDA meeting. Here's Ed Kaye, "Most of the data we have submitted I think the as I said, really the focus one of the things that was not placed into the briefing documents as in the fourth biopsy and so that will be a discussion if that’s allowed by the FDA that will be certainly be something that we will have a discussion point about". Earlier in the article he reports that all the 4th biopsies have been conducted. Kaye's plan to discuss the 4th biopsies at the in-person pre-NDA meeting is a fact. They are all completed and we are expected to believe that the details of the 4th biopsies were not discussed at pre-NDA meeting.
Dated 6/2/15 excerpt: "The FDA consistently said it would be necessary to include data in its NDA demonstrating that eteplirsen increases production of the muscle protein dystrophin. Regulatory agents said they were concerned the measurements were not adequately robust to support an NDA submission. But the relationship between the company and the FDA took a huge step forward 11 days ago after the company presented a new and detailed data package to the regulatory agency. The company plans to submit total components required by the regulatory agency by mid-2015". This comment was in reference to dystrophin production and methodology. The company submitted new data and their relationship with the FDA changed dramatically. When I have time i will post hayes quotes on subject.
Simp, You are incorrect. Kaye has made statements in 2 different instances and when read together he states [paraphrase] exactly what I have reported. This has already been rehashed ad nauseum not only on this post but on IV. Take your BS somewhere else
dylacha, SRPT hasn't released the results to the public, yet. They were shared with the FDA at their pre-NDA meeting. Ed Kaye has referenced this and he stated that this should alleviate the FDA's fears about dystrophin production and quantification. Investors should expect greater then 10% in all 11 patients.
mI expert, I do have a couple I like based on the strength of their chemistries but they are so over valued right now I wouldn't recommend them. I'm currently checking out 2 small cap drug development incubators and when I have something concrete I'll post it.
Ru, "This type of post-hoc reasoning demonstrates a misunderstand of the fundamentals of standard clinical trial practices" I would agree with your statement except for instances where it is proven, for the first time, that a drug patches over a targeted mRNA transcript goes through the translational and protein construction pathways and then has to be incorporated into structural cytoskeletal and membrane networks. When ever a biotech company is pushing new boundaries it is up to that company to educate and convince the regulators of the quality of their endpoints, methodologies for measuring these biomarkers and the expected clinical effect timeline.
Sentiment: Strong Buy
Ru, Your statement, "Two subjects were omitted from the reporting in company PRs and a scientific journal article. Whether they can be omitted from the analysis submitted to the FDA is highly doubtful" Your comment would be accurate[ omitting from analysis ] if SRPT couldn't prove that cellular amelioration and clinical efficacy scores began to have a measurable effect post 24 weeks of treatment. Each patient, including the 2 boys dropped from analysis clearly have measurable positive effects. It's the job of SRPT's adcom participants to convince the panel that this is a fact. This is why I would love for ed kaye to invite Summerton and Wilton to address the oligo chemistries differences and the significant reduction eteplirsen has on biomarkers and clinical decline.
2 boys were initially omitted from analysis because they lost ambulation before treatment effect kicked in [24-36 weeks]. They continued treatment and post-36 weeks stabilized course of their disease
squirrel, I didn't mean to convey that the panel will be stacked with all pediatric neurologists that all had an honorable agenda. they will be experts in the field but I have seen on many panels physicians vote against what was obviously best for the patients. Sometimes it's a head scratcher.
Normally you would be right but in this case the FDA is giving Sarepta 60 days post June 30th to submit Phase III safety data. SRPT can petition the FDA to submit any additional data that supports their application.
Carrix, The probability of that happening is close to zero. Biomarin finished their submission in late April. Sarepta's NDA submission will be mostly completed by June 30th. Add another 2 months for Phase III safety data and If Kaye decides to submit 36 week efficacy from the Phase III now we are talking late Sept. early Oct for the complete submission . BMRN could go as early as early August. Why would the FDA delay BMRN's application til Oct/Nov.???
Adcom in Oct/Nov then vote. Panel of pediatric neurologists that specialize in DMD will overwhelmingly approve. This will be "de-facto" approval because the FDA body will never over rule these DMD experts.
cont'd: Biomarin on the other hand must data mine from 2 different trials that their 5-7 yo cohorts performed slightly better [no statistical significance] then their peers. The 5-7 yo historical data contains great variability on the overall progression of clinical symptoms in this cohort. It is difficult to support Biomarin's supposition that this cohort benefitted from Drisa. If science and statistical evidence rules the day the FDA cannot support approval of Drisa. The should conclude that Biomarin's supposition supports conducting another trial, not approval. Does anyone want to place a bet on if this happens that Biomarin will never run another Drisa trial??
SRPT investors should not wish for an eteplirsen adcoms on the same day as Biomarin's Drisa for several reasons. If I was Ed Kaye I would invite Jim Summerton or Steve Wilton to lead off their adcom presentation with the molecular differences between the 2 radically different chemistries. Summerton is the inventor of the PMO which he began to design in the late 1970's. He designed it because he foresaw the chemical limitations of Cy steins S-DNA's. Steve Wilton would present scientific dat on how he tested in his UWA lab the 3 or 4 main oligo chemistries in use today in his early DMD studies. His results revealed that the PMO overwhelmingly outperformed the competing chemistries. These presentations are needed to highlight the superiority of the PMO thereby creating separation from Drisa. Next I would present the overwhelming evidence that biomarkers were significantly effected by eteplirsen therapy. There are hundreds of these biomarkers that are linked to an overall amelioration at the cellular level. The obvious ones are dystrophin, which is SRPT's primary endpoint [surrogate], creatine kinase levels, inflammatory mediators etc.. Biomarin on the other hand can not produce clinical evidence that's persuasive to the adcom regulators. More separation. Thirdly, 6MWT scores. SRPT can demonstrate across their treatment cohort that all patients scored better then a matching historical cohort. Many critics of this data mention the 2 boys removed from this cohort. This is a red herring because there is significant data that clinical improvement from oligo therapy takes 6-8 months to have measurable clinical effect. I have posited this probability for years. Since the two boys lost ambulation prior to this time period it is scientifically and statistically sound to omit these two boys. Once these 2 boys lost ambulation they began to show clinically manful stabilization like pulmonary function scores. In many cases overall there has been improvement of Fx. Biomarin on the o
Sentiment: Strong Buy
Gary, BMRN's Drisa doesn't deserve to be approved in humans. The FDA guidance strongly correlates with SRPT's Primary endpoint, dystrophin, but intermediate endpoints like pulmonary function and other biomarkers. Couple this with 6MWT scores above the historical norm and I'm feeling extremely confident. Let's apply FDA's new guidance with Drisa. FDA downgrades the importance of 6MWT scores and upgrades biomarkers. The only endpoint that BMRN can hang it#$%$ on is one PhaseII 24 week 6MWT score. Nevermind that it was never duplicated in follow-up testing and completely failed to reach significance in the confirmatory Phase III trial. The only chance BMRN has if the FDA wants to get political in this process. If it does the FDA should be disbanded.
Sentiment: Strong Buy
immediate, What I find interesting in the FDA's guidance is that approval can be based on pulmonary Fx. scores. Pulmonary Fx is not an endpoint in the design of the PhaseII. It is an intermediate marker. Sounds like improved dystrophin scores plus improvement in pulmonary Fx amounts to a slam dunk for AA. This doesn't take into account 6MWT scores that are better then historical cohort. If I was "short" I would need a nice stiff drink about now.